Gene therapy, the insertion of therapeutic genes into a patient~s cells, has been proposed as a treatment for many diseases, both inherited and infectious. Most current approaches have used viruses as vectors for gene delivery, taking advantage of the virus's ability to efficiently infect its target cell. However, formidable obstacles must be overcome before viral-mediated gene delivery can become a useful therapy. Some of these obstacles include: efficient infection of target cells, particularly primary cells; regulated gene expression after delivery; and long-term, tissue-specific gene expression. Herpes simplex virus (HSV) vectors have been proposed as vectors for gene therapy because of their large capacity for foreign genes, their extended host range, and their ability to infect post-mitotic cells. In fact, replication-incompetent HSV vectors may be especially well suited for gene delivery to non- dividing cells. We have developed replication-incompetent HSV vectors for gene delivery, and shown that one such vector that expressed human interferon alpha dramatically inhibited human immunodeficiency virus (HIV) replication in human monocytes. Interferon delivery in this manner arrested HIV replication even if HIV had already spread through much of the monolayer. Although interferon gene expression was transient, the vector remained in a recoverable form for extended periods after delivery. These results suggest that similar replication-incompetent HSV vectors might be designed that either can deliver therapeutic genes for extended periods, or be induced to express a therapeutic gene at a critical point in time. Current research is exploring the use of the HIV LTR as an inducible promoter in replication-incompetent HSV vectors.